individualized tumor specific tcr- t cells in the treatment of advanced solid tumors

Conditions: Solid Tumor

Summary: the primary purpose of this study is to evaluate the safety of the tumor-specific tcr-t cells in the treatment of advanced solid tumor . the secondary purpose of this study is to preliminarily showed the effect of tcr-t cells in the treatment of advanced solid tumor .

this study is an open, single-center, phase i clinical trial which is aim to evaluate the safety and tolerability of tumor-specific tcr-t cells. in this study, these tcr-t cells will be multiplied, or grown, in the laboratory.subjects will received tcr-t cells infusions twice at day 0 and day 14, with the use of il-2 for 5 consecutive days after every cell infusion.

Eligibility criteria:
inclusion criteria: 1. aged between 18 and 70 years old, regardless of gender; 2. diagnosed as solid tumors by histopathology, and the tumor lesions could be detected or evaluated; 3. be after standard treatment or who lack effective treatment programs; 4. patients and their families were willing to participate in the clinical trial and signed the informed consent; 5. physical status: ecog score 0-1; 6. expected survival time \> 3 months; 7. hiv antibody negative;hepatitis b surface antigen negative;hepatitis c antibody negative;the results of blood routine and coagulation were roughly normal, lymphocyte \>0.8×10\^9/l, hemoglobin \>100g/l, and the pregnancy test of female patients with fertility potential was negative. 8. left ventricular ejection fraction 50% as indicated by cardiac ultrasound;upper normal level of serum alt/ast \< 2.5 times;serum creatinine 1.6mg/dl;total bilirubin 1.5mg/dl, subject's total bilirubin \< 3mg/dl except for gilberts syndrome; 9. at least 4 weeks after the last systemic treatment, the patient's toxic and side effects must be restored to grade 1 or lower (except for alopecia or vitiligo).if the subject undergoes minor surgery within 3 weeks prior to enrollment, as long as all toxicity is recovered to level 1 or lower, the subject will meet the enrollment requirements. 10. during the whole study period, patients can regularly visit the enrolled research institutions for relevant detection, evaluation and management; 11. the patient is not allowed to use any anti-tumor drugs or treatments for 4 weeks prior to the infusion of tcr-t cells; 12. patients' tumor lesions can be obtained by surgery or puncture, and tumor infiltrating t cells can be successfully isolated from the obtained tumor tissue; 13. t cells in patients' peripheral blood can effectively proliferate and expand by at least 10 times in the pre-culture; 14. the benefits of participating in the clinical trial outweigh the risks,which was evaluated by the researchers base on the status or condition of the patients. exclusion criteria: 1. any form of primary immunodeficiency disease (such as severe combined immunodeficiency disease); 2. experiencing moderate to severe infection or possible opportunistic infection; 3. patients with a history of autoimmunity (e.g., sle, psoriasis, etc.); 4. acute systemic infection, coagulation dysfunction or other serious cardiopulmonary diseases; 5. patients who have is suffering a large amount of glucocorticoid or other immunosuppressive agents within 4 weeks; 6. be allergic to any drug used in this study; 7. central nervous system metastases patients with clinically unstable or acute meningitis (except these clinically stable after treatment) clinical stability needs to be met as follows: 4 weeks at least before the trial treatment, 1) no new brain lesion or no expanded of the original lesions confirmed by mri); 2) no hormone therapy for at least 2 weeks; 3) neurological symptoms have returned to baseline; 8. pregnant and lactating women, as well as male and female patients who could not cooperate with contraception during the study period.

Keywords: tcr-t